Renal transplantation across the ABO barriers was found, already in the early days of transplantation, to result in a high incidence of transplants that never functioned, and it was therefore regarded as a prerequisite in allotransplantation to comply with the traditional Landsteiner rules used for blood transfusion. The recipient's preformed anti-A/B isoagglutinins are responsible for hyperacute rejection of ABO-incompatible grafts. This hyperacute rejection is similar to that seen in alloimmunized patients with donor-reactive HLA-antibodies. The first trial to cross the ABO barrier in transplantation was started in the early 1970's grafting blood group A2 cadaveric kidneys to O recipients.1 In the 1980's, using A1 and B donors Alexandre performed the first series of ABO incompatible living donor (LD) renal transplantations and obtained graft survival similar to those of ABO compatible cases. The immunosuppressive protocol encompassed pre-operative plasmapheresis to remove anti-A/B antibodies, donor platelet transfusion, splenectomy and induction therapy with anti-lymphocyte/thymocyte globulin, injection of blood group A or B substances extracted from porcine stomach and Cyclosporine-Azathioprine-prednisone. Since then, more than 500 cases of ABO incompatible LD renal transplantations have been reported worldwide, mainly from Japan (reviewed in 1), and the importance of reducing recipient anti-A/B antibody levels before grafting to avoid rejection has been well documented.2,3 The graft survival in these series is good (1 year graft survival of about 85% for A1 and B donors) but slightly inferior to that of ABO compatible grafts due to single cases with severe anti-A/B antibody mediated rejection.4,5 Recent data on ABO incompatible renal transplantations using an anti-CD20 antibody (Rituximab) combined with antibody removal were shown to be even better with regard to graft survival6,7. 
In times of severe organ shortage, an increased use of grafts from ABO incompatible donors will allow more LD kidney transplantations to be performed. In addition, the experience gained in this field will also be applicable on the pre-treatment and post-transplant management of HLA-sensitized patients.8 